Figure 1. TGF-β-signaling causes metabolic reprogramming in CAFs to promote tumorigenesis. Cancer cells secrete TGF-β that initiates the conversion of mammary stromal fibroblasts to myofibroblasts in a paracrine fashion. During the series of tumor progression, myofibroblasts increase their TGF-β production and conversely decrease Cav-1 expression. The resulting myofibroblasts activate TGF-β signaling in an autocrine fashion, which leads to increased oxidative stress, induction of autophagy/mitophagy and subsequently aerobic glycolysis (Warburg effect), thereby generating metabolites (lactate, pyruvate, glutamine, ketone bodies, etc.). These metabolites, which are routed to the adjacent cancer cells, boost their anabolic metabolism and growth.